In the United States, it is estimated that 11,000 individuals sustain spinal cord injuries each year. One major factor that limits treatment of spinal cord injury is the failure of axons to regenerate spontaneously after central nervous system (CNS) injury. Regeneration failure can be partially attributed to a limited intrinsic axon growth capacity of adult neurons. Indeed, augmenting the growth potential of centrally projecting axons via peripheral conditioning or other cAMP-dependent mechanisms improves axonal regeneration. Likewise, delivery of neurotrophins results in comparable gains. In addition to a limited growth capacity, an inhospitable extracellular environment hinders regeneration. Moderate microtubule stabilization increases the regeneration ability of axons at the same time that it decreases the inhibitory properties of scar tissue. Other therapeutic interventions that neutralize inhibitors associated with residual myelin or chondroitin-sulfate proteoglycan, a scar-associated inhibitor, also lead to improvements in axonal regeneration. Despite observations of only modest gains (˜500 μm) using pharmacological therapies, neurons within the CNS can achieve long distance axonal regeneration.
After it was demonstrated that CNS axons have the ability to regenerate into PNS grafts, it has been found that long distance regeneration can be obtained using this approach. Within peripheral nerve grafts, parallel columns of Schwann cells surrounded by basal lamina (bands of Büngner) render excellent guidance to regenerating axons. However, harvesting autografts is limited by tissue availability and donor site morbidity, and the alternative acellularized allografts fail to support axonal regeneration. To mimic the favorable attributes of peripheral nerve grafts, several groups have used Schwann cells and topographic/chemotropic guidance cues to support regeneration. Nevertheless, poor survival limits the potential of cellular therapies, and neurotrophin administration requires precise timing, dose, and spatial distribution.
As such, there is currently no cure for spinal cord injury and there exists a need for scaffolds capable of promoting neural regeneration.